The handling, mixing and delivery of bulk solids present unique difficulties when the solids are handled in powdered form. Often, one or more physical properties of the powdered particulates themselves are important, or even critical, to the application for which the composition is intended. Particulate shape, particulate size and particulate porosity often describe important physical properties or characteristics. Environmental conditions (humidity, temperature, shear forces among others) encountered by a powder during use or storage can and often do affect one or more properties of the particulates. Aggregation, agglomeration, attrition and flocculation represent the most common degradative effects on a powder and their presence or progression greatly limits the utility and viability of many powder compositions.
Achieving a uniform blend of dry bulk solids is a problem faced daily by engineers and operators in industries as varied as pharmaceuticals, foods, plastics and battery production. Even when an acceptable blend is obtained additional challenges arise in maintaining the blend through one or more pieces of downstream equipment. Poor blending or the inability to maintain an adequate blend before and during processing lead to additional and unnecessary costs, including costs associated with rejected material and decreased yields, added blending time and energy, decreased productivities, start-up delays and defective or out-of-specification products. Powder caking of raw and in-process materials, particularly during storage (in, e.g., bags or drums) can also pose significant problems. Both powder caking and an inability to achieve uniform blends and mixtures can decrease batch uniformity which, among other drawbacks, can require increased testing and sampling. In pharmaceutical applications, batch disuniformities translate directly to dose disuniformities.
Some flowability aids are known. Fumed silica, for example, is one popular powder additive that can be used to improve flow characteristics. While relatively inexpensive, fumed silica often is ineffective in preventing agglomeration of many particle types. Flowability is also a matter of degree; many, if not most, uses of fumed silica lead to some agglomeration and aggregation. Some undemanding industrial applications can tolerate a level of agglomeration not tolerated in more demanding applications. Applications involving precise metering or mixing of a powder, however, require more. Even in relatively undemanding applications the ability to improve powder flow can provide an increase in homogeneity with milder mixing conditions or with reduced mixing periods. Additionally, increased powder flowabilities can allow utilization of lower levels of expensive ingredients, e.g., dyes and pigments, particularly where the required level of such ingredients correlates with the dispersibility of the materials in the powder with which they are mixed.
The preparation or delivery of pharmaceutical drugs and medicaments as powders is particularly demanding. Pharmaceutical applications must take careful account of various particle or powder characteristics, and pharmaceutical compositions often are prepared as powders as an intermediate step to final formulation in myriad forms for delivery to the patient. Pharmaceutical compositions can be tabletted or encapsulated for oral gastro-intestinal ingestion and delivery. They also can be incorporated into a dry powder inhaler (DPI) for delivery to the respiratory tract. The ability to achieve homogeneous blends of compositions containing relatively low levels (by weight) of pharmaceutically active ingredients is very difficult.
Recent advances in improving the flowability characteristics of powders by adding surface-modified nanoparticles are disclosed in International Publication WO 2007/019229, entitled “Compositions Exhibiting Improved Flowability” (incorporated herein by reference). However, there are significant challenges in handling surface-modified nanoparticles and in manufacturing powder formulations, such as medicament powder formulations, having surface-modified nanoparticles therein.